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Ginsenoside Rd ameliorates colitis by inducing p62-driven mitophagy-mediated NLRP3 inflammasome inactivation in mice.

Authors
  • Liu, Chao1
  • Wang, Jianing2
  • Yang, Yan3
  • Liu, Xiuting4
  • Zhu, Yubing1
  • Zou, Jianjun1
  • Peng, Sishi5
  • Le, Thi Ha1
  • Chen, Yu1
  • Zhao, Shuli6
  • He, Bangshun6
  • Mi, Qiongyu6
  • Zhang, Xu7
  • Du, Qianming8
  • 1 Department of Pharmacy, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, PR China; Department of Clinical Pharmacy, School of Basic Medicine & Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China. , (China)
  • 2 Neurobiology Laboratory, Jiangsu Center for Drug Screening, China Pharmaceutical University, Jiangsu, Nanjing 210009, China. , (China)
  • 3 Department of Pharmacy, The Third People's Hospital of Chengdu & Affiliated Hospital of Southwest Jiaotong University, 82 Qing Long Street, Chengdu 610031, China. , (China)
  • 4 Department of Clinical Pharmacy, School of Basic Medicine & Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China. , (China)
  • 5 General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, PR China; Department of Clinical Pharmacy, School of Basic Medicine & Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China. , (China)
  • 6 General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, PR China. , (China)
  • 7 Department of Medicine, The First People's Hospital of Chengdu & Affiliated Hospital of Chengdu Medical College, 18# Wanxiang East Road, Chengdu 610041, China. Electronic address: [email protected] , (China)
  • 8 General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, PR China; Department of Clinical Pharmacy, School of Basic Medicine & Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Biochemical pharmacology
Publisher
New York, NY : Elsevier Science Inc
Publication Date
Sep 01, 2018
Volume
155
Pages
366–379
Identifiers
DOI: 10.1016/j.bcp.2018.07.010
PMID: 30012462
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Previous studies reported that Ginsenoside Rd (Rd) had anti-inflammatory and anti-cancer effects. However, the molecular mechanism underlying the inhibition effect of Rd on colitis in mice hasn't been clarified clearly. Here, in our study, we detected the effects of Rd on dextran sulfate sodium (DSS)-induced murine colitis, and found that oral administration of Rd dose-dependently alleviated DSS-induced body weight loss, colon length shortening and colonic pathological damage with lower myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities and higher glutathione level. In addition, the production of pro-inflammatory cytokines (IL-1β, TNF-a and IL-6) in both serum and colonic tissues were significantly down-regulated by Rd administration. The activation of NLRP3 inflammasome was also suppressed in Rd-treated group, resulting in reduced caspase-1 production and IL-1β secretion. In vitro, Rd remarkably inhibited NLRP3 inflammasome activation which was mostly dependent on the mitochondrial translocation of p62 and mitophagy. Importantly, Rd-driven inhibition of the NLRP3 inflammasome was significantly blocked by various autophagy inhibitors. Furthermore, upregulation of AMPK/ULK1 signaling pathway accounted for Rd-induced autophagy, which was also seen in vivo. In conclusion, our results demonstrated the function of Rd on the inhibition NLRP3 inflammasome and its potential application for the treatment of NLRP3-associated diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

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